Dimethylformamide → N-Methoxy-N-methyl-5-ethyl-1-methylpyrazole-3-carboxamide

HRID 1825360Notes

Reaction equation

HRID 1825360 reaction equation
[CH2:1]([C:3]1[N:7]([CH3:8])[N:6]=[C:5]([C:9]([OH:11])=O)[CH:4]=1)[CH3:2].[CH3:12][N:13](C=O)C.[C:17](Cl)(=[O:21])C(Cl)=O>ClCCl>[CH3:17][O:21][N:13]([CH3:12])[C:9]([C:5]1[CH:4]=[C:3]([CH2:1][CH3:2])[N:7]([CH3:8])[N:6]=1)=[O:11]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 199675945-ethyl-1-methyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 19967595N-Methoxy-N-methyl-5-ethyl-1-methylpyrazole-3-carboxamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

5-Ethyl-1-methylpyrazole-3-carboxylic acid (2.5 g) in dichloromethane (50 ml) was treated with DMF (0.12 ml) and cooled under argon in an ice-bath. The solution was treated with oxalyl chloride (2.2 g) in dichloromethane (25 ml) in a dropwise fashion. After complete addition the reaction mixture was maintained at 0° C. for 25 min. and then allowed to warm to room temperature. The solution was evaporated and the residue re-dissolved in toluene (100 ml) and concentrated again. The crude acid chloride was taken up in dichloromethane (50 ml), and treated with N,O-dimethylhydroxylamine hydrochloride (1.72 g), cooled in an ice-bath and pyridine (2.86 ml) added. The reaction mixture was allowed to stir at room temperature for 2 h. The reaction mixture was washed with brine, dried over anhydrous magnesium sulphate and concentrated to an oil. The product was purified by ‘flash’ silica gel chromatography to give the title compound as a yellow oil, (2.995 g, 94%); (Found: M+, 197.1167. C9H15N3O2 requires M, 197.1164); nmax (CH2Cl2) 1640, 1484 and 1374 cm−1; dH(CDCl3) 1.28 (3H, t, J7.5 Hz), 2.62 (2H, q, J7.5 Hz), 3.43 (3H, s), 3.76 (3H, s), 3.83 (3H, s) and 6.72 (1H, s).

Workup

  1. temperaturecooled under argon in an ice-bath
  2. additionAfter complete addition the reaction mixture
  3. temperatureto warm to room temperature
  4. customThe solution was evaporated
  5. dissolutionthe residue re-dissolved in toluene (100 ml)
  6. concentrationconcentrated again
  7. additiontreated with N,O-dimethylhydroxylamine hydrochloride (1.72 g)
  8. temperaturecooled in an ice-bath
  9. additionpyridine (2.86 ml) added
  10. washThe reaction mixture was washed with brine
  11. dry with materialdried over anhydrous magnesium sulphate
  12. concentrationconcentrated to an oil
  13. customThe product was purified by ‘flash’ silica gel chromatography

Sources & evidence

ORD record
ord-08db40ef592f438eb1fbee937f757791
Source dataset
uspto-grants-2006_05
Patent number
US07045619B2

Reaction notes

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